Safety and Effectiveness of Lopinavir/Ritonavir in HIV Infected Infants

NCT00038480 | Completed Phase 1

• 3 other identifiers: P103010041PACTG P1030
• Study Type: interventional
• Target: 31
• Locations: 3 countries
• Sites: 17

Brief Summary

The purpose of this study is to find out if the drug lopinavir/ritonavir (LPV/RTV) is safe and well tolerated in HIV infected infants. This study will also determine the most effective dose of LPV/RTV for infants.

Conditions

HIV Infections

Keywords

Lopinavir; HIV-1; Drug Therapy, Combination; HIV Protease Inhibitors; Ritonavir; Reverse Transcriptase Inhibitors

Outcome Measures

Primary Outcomes (2)

• Trough concentration of LPV and pharmacokinetic parameters

  Weeks 8, 16, 24, 36, 48, 60, 72, 84, and 96

• Recurrent treatment-related Grade 3 and non-life threatening Grade 4 toxicity or single occurence of life-threatening Grade 4 toxicity

  Throughout study

Secondary Outcomes (3)

• Change in CD4 and CD8 count and percentage from baseline. HIV-1 specific CD4 count and CD8 mediated and humoral responses

  Study entry and Weeks 12, 24, 36, 48, 60, 72, 84, and 96

• Time to virologic failure

  Throughout study

• Suppression of viral load to less than 400 copies/ml and less than 50 copies/ml

  Study entry and Weeks 2, 4, 8, 12, 16, 20, 24, 32, 36, 40, 48, 60, 72, 84, and 96

Interventions

Lopinavir/Ritonavir DRUG

Eligibility Criteria

• Age: 14 Days - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• HIV infected
• Viral load greater than 10,000 copies/ml within 30 days prior to study entry
• Weigh more than 5.5 lbs at the time of enrollment
• Agree to take 2 nucleoside reverse transcriptase inhibitors (NRTIs) in addition to LPV/RTV
• Have consent of parent or guardian willing to provide signed informed consent and to have the infant followed at a PACTG site

You may not qualify if:

• Currently taking a nonnucleoside reverse transcriptase inhibitor or protease inhibitor (PI) while on study
• Previously used LPV/RTV. Patients who were treated previously with other PIs are not excluded. Prior or concurrent maternal treatment with LPV/RTV is not excluded.
• For patients less than 6 weeks old at time of enrollment, less than 34 weeks gestation at delivery OR for patients 6 or more weeks old at time of enrollment, less than 32 weeks gestation at delivery
• Any laboratory toxicity of Grade 3 or greater. Hyperlipasemia of Grade 2 or higher is also excluded.
• Newly diagnosed acute opportunistic or serious bacterial infection requiring therapy at the time of enrollment
• Chemotherapy for active cancer
• Certain medications
• Any other clinically significant conditions, other than HIV infection, that would interfere with the study

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (17)

Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.

Oakland, California, 94609-1809, United States

Location

UCSF Pediatric AIDS CRS

San Francisco, California, 94143-0105, United States

Location

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, 80218-1088, United States

Location

Children's National Med. Ctr. Washington DC NICHD CRS

Washington D.C., District of Columbia, United States

Location

Univ. of Florida Jacksonville NICHD CRS

Jacksonville, Florida, 32209, United States

Location

USF - Tampa NICHD CRS

Tampa, Florida, United States

Location

Chicago Children's CRS

Chicago, Illinois, 606143394, United States

Location

Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases

Baltimore, Maryland, 21287, United States

Location

Children's Hosp. of Boston NICHD CRS

Boston, Massachusetts, 021155724, United States

Location

Baystate Health, Baystate Med. Ctr.

Springfield, Massachusetts, 01199, United States

Location

Bronx-Lebanon Hosp. IMPAACT CRS

The Bronx, New York, 10457, United States

Location

St. Christopher's Hosp. for Children

Philadelphia, Pennsylvania, United States

Location

St. Jude/UTHSC CRS

Memphis, Tennessee, 381052794, United States

Location

SOM Federal University Minas Gerais Brazil NICHD CRS

Minas Gerais, Brazil

Location

Univ. of Sao Paulo Brazil NICHD CRS

São Paulo, Brazil

Location

San Juan City Hosp. PR NICHD CRS

San Juan, Puerto Rico

Location

Related Publications (8)

• Luzuriaga K, Wu H, McManus M, Britto P, Borkowsky W, Burchett S, Smith B, Mofenson L, Sullivan JL. Dynamics of human immunodeficiency virus type 1 replication in vertically infected infants. J Virol. 1999 Jan;73(1):362-7. doi: 10.1128/JVI.73.1.362-367.1999.

  PMID: 9847340 BACKGROUND

• Equils O, Garratty E, Wei LS, Plaeger S, Tapia M, Deville J, Krogstad P, Sim MS, Nielsen K, Bryson YJ. Recovery of replication-competent virus from CD4 T cell reservoirs and change in coreceptor use in human immunodeficiency virus type 1-infected children responding to highly active antiretroviral therapy. J Infect Dis. 2000 Sep;182(3):751-7. doi: 10.1086/315758. Epub 2000 Aug 15.

  PMID: 10950768 BACKGROUND

• Luzuriaga K, McManus M, Catalina M, Mayack S, Sharkey M, Stevenson M, Sullivan JL. Early therapy of vertical human immunodeficiency virus type 1 (HIV-1) infection: control of viral replication and absence of persistent HIV-1-specific immune responses. J Virol. 2000 Aug;74(15):6984-91. doi: 10.1128/jvi.74.15.6984-6991.2000.

  PMID: 10888637 BACKGROUND

• Saez-Llorens X, Violari A, Deetz CO, Rode RA, Gomez P, Handelsman E, Pelton S, Ramilo O, Cahn P, Chadwick E, Allen U, Arpadi S, Castrejon MM, Heuser RS, Kempf DJ, Bertz RJ, Hsu AF, Bernstein B, Renz CL, Sun E. Forty-eight-week evaluation of lopinavir/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2003 Mar;22(3):216-24. doi: 10.1097/01.inf.0000055061.97567.34.

  PMID: 12634581 BACKGROUND

• Chadwick EG, Pinto J, Yogev R, Alvero CG, Hughes MD, Palumbo P, Robbins B, Hazra R, Serchuck L, Heckman BE, Purdue L, Browning R, Luzuriaga K, Rodman J, Capparelli E; International Maternal Pediatric Adolescent Clinical Trials Group (IMPAACT) P1030 Team. Early initiation of lopinavir/ritonavir in infants less than 6 weeks of age: pharmacokinetics and 24-week safety and efficacy. Pediatr Infect Dis J. 2009 Mar;28(3):215-9. doi: 10.1097/INF.0b013e31818cc053.

  PMID: 19209098 RESULT

• Chadwick EG, Yogev R, Alvero CG, Hughes MD, Hazra R, Pinto JA, Robbins BL, Heckman BE, Palumbo PE, Capparelli EV; International Pediatric Adolescent Clinical Trials Group (IMPAACT) P1030 Team. Long-term outcomes for HIV-infected infants less than 6 months of age at initiation of lopinavir/ritonavir combination antiretroviral therapy. AIDS. 2011 Mar 13;25(5):643-9. doi: 10.1097/QAD.0b013e32834403f6.

  PMID: 21297419 RESULT

• Persaud D, Palumbo PE, Ziemniak C, Hughes MD, Alvero CG, Luzuriaga K, Yogev R, Capparelli EV, Chadwick EG. Dynamics of the resting CD4(+) T-cell latent HIV reservoir in infants initiating HAART less than 6 months of age. AIDS. 2012 Jul 31;26(12):1483-90. doi: 10.1097/QAD.0b013e3283553638.

  PMID: 22555165 DERIVED

• Persaud D, Palumbo P, Ziemniak C, Chen J, Ray SC, Hughes M, Havens P, Purswani M, Gaur AH, Chadwick EG; Pediatric AIDS Clinical Trials Group P1030 Team. Early archiving and predominance of nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 among recently infected infants born in the United States. J Infect Dis. 2007 May 15;195(10):1402-10. doi: 10.1086/513871. Epub 2007 Apr 5.

  PMID: 17436219 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Lopinavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ellen G. Chadwick, MD

  Children's Memorial Hospital, Division of Pediatric Infectious Diseases

  STUDY CHAIR

• Jorge Pinto, MD, DSc

  Escola de Medicine, Universidade Federal de Minas Gerais

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2002
• First Posted: June 3, 2002
• Study Completion: September 1, 2007
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

US (14); BR (2); PR (1)